Synthesis and Antioxidant Evaluation of Some Novel Thiophene, Pyrazole, Chromene, Pyrazolotriazine Derivatives Bearing Sulfonamide Moiety

Article abstract of DOI:10.1002/jhet.2576

As a part of ongoing studies in developing new potent antioxidant agents, N-[4-(aminosulfonyl)phenyl]-2-cyanoacetamide (3) was utilized as key intermediate for the synthesis of some new thiophene, chromene, and pyrazolotriazine pyridine derivatives. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR,¹H-NMR, and mass spectral data. Representative compounds of the synthesized products were tested and evaluated as antioxidant. Compounds 7 and 30 are promising compounds.

Full text of DOI:10.1002/jhet.2576

Month 2015
Synthesis and Antioxidant Evaluation of Some Novel Thiophene,
Pyrazole, Chromene, Pyrazolotriazine Derivatives Bearing
Sulfonamide Moiety
Moustafa A. Goudaa,b
*
aDepartment of Chemistry, Faculty of Science and Arts, Ulla, Taibah University, Medina, Saudi Arabia
bDepartment of Chemistry, Faculty of Science, Mansoura University, El-Gomhoria Street, 35516, Mansoura, Egypt
*
E-mail: dr_mostafa_chem@yahoo.com
Received September 19, 2015
DOI 10.1002/jhet.2576
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
As a part of ongoing studies in developing new potent antioxidant agents, N-[4-(aminosulfonyl)phenyl]-2-
cyanoacetamide (3) was utilized as key intermediate for the synthesis of some new thiophene, chromene, and
pyrazolotriazine pyridine derivatives. The structures of the newly synthesized compounds were confirmed by
elemental analysis, IR, 1H-NMR, and mass spectral data. Representative compounds of the synthesized
products were tested and evaluated as antioxidant. Compounds 7 and 30 are promising compounds.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
exhibit diverse pharmacological properties such as anticancer
[20], anticoagulant, estrogenic, dermal, photosensitizing,
antimicrobial, vasodilatory, molluscicidal, antihelminthic,
sedative, hypnotic, analgesic hypothermic [21,22], and free
radical-scavenging activities, especially of the superoxide
anions generated by activated neutrophils [23]. Moreover,
many biological properties for triazine derivatives have been
reported such as herbicidal [24], antimicrobial [25], anti-HIV
[26], anticancer agents [27], and antioxidant [28].
In view of these facts and as a continuation of our
research program on the chemistry of cyanoacetamide
[28–30], the present investigation aimed to synthesize
and characterize newer thiophene, chromene, acrylamide,
pyrazole, hydrazones, and pyrazolotriazine incorporating
sulfonamide moiety in order to evaluate their antioxidant
activities. It was found that N-[4-(aminosulfonyl)phenyl]-
2-cyanoacetamide (3) is an excellent building block for
the synthesis of the target objectives.
Cyanoacetamides are polyfunctional compounds having
both electrophilic and nucleophilic properties. These chemi-
cal properties have been utilized to design different heterocy-
clic moiety with different ring sizes such as thiophene,
pyrazole, chromene, and pyrazolotriazine [1]. In addition,
the diverse biological activities reported for many derivatives
of cyanoacetamide have also drawn the attention of biochem-
ists in the last decade; their pharmaceutical activities include
antimicrobial [2], antifungal [3], insulin-releasing [4], anti-
inflammatory [5], and antitumor properties [6]. Sulfonamides
derivatives possess a wide range of biological properties and
they act as antibacterial [7], antifungal [8], anticancer agent
[9], and in Alzheimer’s disease [10]. The investigations
showed that 2-aminothiophene derivatives of different hetero-
cyclic nucleus have shown potent pharmacological proprie-
ties like A1 adenosine receptor allosteric enhancers [11,12],
inhibitors of human leukocyte elastase [13,14], antitumor
[15], and antitumor and anti-HIV activities [11]. Moreover,
piperidines are reported to possess antitumor [16] and antibac-
terial properties [17]. Furthermore, morpholine derivatives
have a wide spectrum of antimicrobial activity and exhibit
anthelmintic, bactericidal, and insecticidal activities [18,19].
Coumarin (2H-chromen-2-one) and its derivatives are
widely distributed in nature and have been reported to
RESULTS AND DISCUSSION
Chemistry. The synthetic strategies adopted to obtain
the corresponding thiophene, pyrazole, chromene, and
pyrazolotriazine derivatives bearing sulfonamide moiety
are depicted in Schemes 1–5. The starting material,
© 2015 HeteroCorporation

M. A. Gouda
Vol 000
Scheme 1. Synthesis of 2-aminothiophenes 6 and 7. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Scheme 2. Synthesis of 4-aminothiophenes 13 and 14.
Scheme 3. Synthesis of acrylonitriles 18, 19, and 20.
N-[4-(aminosulfonyl)phenyl]-2-cyanoacetamide (3), was
prepared in a high yield and purity via cyanoacetylation
of 1 with 3,5-dimethyl-1-cyanoacetyl pyrazole (2) [31]
through the modification of the reported procedure [32]
(Scheme 1).
reacting amide (3) with sulfur and cycloheptanone (4) or
cyclohexanone (5) in the presence of morpholine as a basic
catalyst. An analogous reaction has been reported by
Schellhase et al. [33], whereas the N-[4-(aminosulfonyl)phe-
nyl]-2-cyanoacetamide (3) was condensed with cyclohexa-
none (5) in benzene in the presence of AcOH/AcONH4 to
afford the arylidene derivative (8). Compound 8 gave the
2-Aminothiophene-3-carboxamides (6) and (7) could be
achieved according to the method described by Gewald, by
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Novel Bioactive Sulfonamides
Scheme 4. Synthesis of acrylonitrile 25, 26, and 28.
Scheme 5. Synthesis of coumarin 30 and pyrazolotriazines 39–41.
corresponding aminothiophene (7) upon refluxing with
sulfur in ethanol in the presence of diethyl amine under
Gewald reaction (Scheme 1). The assignment of the structure
of compounds 6 and 7 was based on analytical and spectro-
scopic data. Compound 6, taken as a typical example of
series prepared, revealed absorption bands at 3303 and
3286cmꢀ1 assignable to NH2 and NH groups. The mass
spectrum showed molecular ion peak at m/z 365 correspond-
ing to a molecular formula C16H19N3O3S2 (Scheme 1).
Furthermore, the reactivity of cyanoacetamide (3) towards
isothiocyanate was investigated. Thus, when compound 3
was left to react with phenylisothiocyanate in dimethyl
formamide, in the presence of potassium hydroxide, at room
temperature, followed by acidification, the formed potassium
salt gave the thiocarbamoyl (9) [34]. Heterocyclization of the
intermediate (8) with chloroacetone (10a) or 2-chloro-1-
phenylethanone (10b) under reflux in DMF/TEA furnished
the thiophene derivatives (13) and (14) as the final products
(Scheme 2). Probably, the reaction proceeds via nucleophilic
displacement of the halogen atom to give an S-alkylated
intermediate (11) and (12) followed by nucleophilic attack
of the active methylene of the latter intermediates (11) and
(12) to give aminothiophene derivatives (13) and (14) as
the final products. The structures of the products (13)
and (14) were determined from spectroscopic and elemental
analytical data. Analytical and spectral data of the product
are in agreement with the proposed structure (Experimental
section).
The Knoevenagel condensation of cyanoacetamide (3)
with aromatic aldehydes, namely, terephthalaldehyde (15),
4-(piperidin-1-yl)benzaldehyde (16), and 5-chloro-3-methyl
-1-phenyl-1H-pyrazole-4-carbaldehyde (17) furnished the
corresponding arylidene derivatives (18–20) (Scheme 3).
The structure of compounds 18–20 was elucidated on the
basis of its analytical and spectral data. IR spectrum of
compound 19, taken as a typical example of series prepared,
revealed absorption bands at 3370, 3316, 2210, and
1684cmꢀ1 corresponding to NH2, nitrile, and carbonyl
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M. A. Gouda
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1
Table 1
ABTS antioxidant activity assay of the new compounds.
functions, respectively. Its H-NMR spectrum showed two
singlet signals δ 8.10 and 2.43ppm because of CH of
arylidene and methyl protons, respectively, two broad sig-
nals at δ 6.91 and 10.10ppm because of NH2 and NH
protons, respectively, in addition to aromatic protons at δ
7.40–7.80. Its mass spectrum showed a molecular ion peak
at m/z 441 corresponding to a molecular formula
C20H16ClN5O3S. Treatment of 3 with 5-chloro-3-methyl-
1-phenyl-1H-pyrazole-4-carbaldehyde (16) in DMF in
presence of piperidine (23) or morpholine (24) as a cata-
lyst afforded the piperidine and morpholine derivatives
(25) and (26).
Compound no.
Absorbance of samples (λ)
% inhibition
Control of ABTSa
Ascorbic acid
0.525
0.061
0.418
0.089
0.181
0.055
0.409
0.415
0.495
0.343
0.428
0.282
0.347
0.476
0.047
0.136
0.396
0.232
0.417
0.400
0.394
0.428
0
87.80
16.4
82.2
65.4
89.0
18.2
17
1
3
6
7
13
14
18
19
20
25
26
28
30
35
36
37
38
39
40
41
1
31.4
14.4
43.6
30.6
9.3
89.3
74.0
20.8
53.6
16.6
20.0
21.2
14.4
The IR spectrum of compound 25, taken as a typical exam-
ple of the series prepared, revealed absorption bands at 3338,
3242, 2205, and 1661cmꢀ1 corresponding to NH, nitrile, and
carbonyl functions, respectively. Its 1H-NMR spectrum
showed the piperidine protons at δ 1.16–1.32, 2.05–2.49,
2.94–3.06 in addition to singlet signal at δ 8.18 because of
arylidene proton (CH¼). Furthermore, its mass spectrum
showed a molecular ion peak at m/z 473 (M+–NH3) that is
in agreement with the molecular formula C25H26N6O3S. On
the other hand, condensation of cyanoacetamide (3) with 5-
chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (16)
in ethanol in the presence of ammonium acetate afforded
the corresponding aminopyrazolopyridine (28), on the basis
of elemental analysis and spectral data. Its mass spectrum
showed a molecular ion peak at m/z 473 (M–[NH3+H2])
together with base peak at m/z 172. The formation of 28
is assumed to proceed via the formation of the inter-
mediate 18 followed by nucleophilic displacement of the
halogen atom to give amino intermediate 27, followed
by the situ cyclization to the aminopyridine skeleton
(Scheme 4).
Cyclocondensation of compound 3 with 2-hydroxy-1-
naphthaldehyde (29) in boiling ethanol containing a
catalytic amount of piperidine afforded corresponding
derivative 2-iminocoumarin (30) in high yield (Scheme 5).
IR spectrum of the reaction product (30) revealed the dis-
appearance of cyano absorption band and showed absorp-
tion bands at 3289, 1682, and 1623 cmꢀ1 corresponding
to NH, carbonyl, and C¼N functions, respectively. Its
1H-NMR spectrum showed three broad signals at δ
6.87, 9.22, and 13.05ppm because of 2NH2 and NH pro-
tons, in addition to an aromatic multiple in the region
7.29–8.21 ppm. Its mass spectrum showed a molecular
ion peak at (M+) m/z 393 corresponding to a molecular
formula C20H15N3O4S.
(%) Inhibition = [A (control) ꢀ A (test)/A (control)] × 100.
ABTS, 2,2′-azino-bis (3-ethyl benzthiazoline-6-sulfonic acid).
aABTS: the method used for antioxidant activity.
Table 2
Bleomycin-dependent DNA damage of the investigated compounds.
Compound no.
Absorbance of samples
Ascorbic acid
0.062
0.086
0.098
0.058
0.097
0.099
0.126
0.081
0.171
0.096
3
6
7
19
25
26
30
35
37
spectral data of the product are in agreement with the pro-
posed structure (Experimental section).
Biological assays.
ABTS antioxidant assay.
The
synthesized compounds were screened for their antioxidant
activity using 2,2′-azino-bis(3-ethyl benzthiazoline-6-
sulfonic acid) (ABTS) method that was reported by Lissi
et al. [38]. The antioxidant activity assay employed here is
one of the several assays that depends on measuring the
consumption of stable free radicals, that is, evaluate the free
radical-scavenging activity of the investigated component.
The methodology assumes that the consumption of the
stable free radical (X′) will be determined by the following
reactions:
Finally, compound 3 was used to synthesize the
pyrazolotriazine derivatives (39–41) via coupling with the
corresponding 3-pyrazole diazonium chlorides (35–38)
[35–37], followed by heating the formed hydrazones
(35–37) in acetic acid (Scheme 5). The structures of the
products 35–38 and 39–41 were determined from spec-
troscopic and elemental analytical data. Analytical and
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Month 2015
Novel Bioactive Sulfonamides
Figure 1. Structures–activity relationship of the more potent antioxidant compounds.
XH þ Y′ → X′ þ YH
The protective activity against DNA damage induced by
the bleomycin–iron complex was examined in order to show
the action of the more potent compounds 3, 6, 7, 19, 25, 26,
30, 35, and 37. The results in Table 2 showed that com-
pounds most of the investigated compounds showed similar
and higher antioxidant activity than ascorbic acid and exhib-
ited high protection against DNA damage induced by the
bleomycin–iron complex, thus, diminishing chromogen for-
mation between the damaged DNA and TBA molecules.
Structure–activity relationships (SAR) of the more
potent antioxidant compounds. Comparing the results ob-
tained for the antioxidant properties of the compounds re-
ported in this study with their structures, the following
SAR are postulated (Fig. 1): (i) it seems that the hydrazone
moieties within 35–38 play an important role in the antiox-
idant activity, as their elimination through cyclization of
the hydrazone derivatives (36–38) into the triazine deriva-
tives (39–41) leads to a decrease in activity. (ii) Compound
3 is more potent than compound 1, which may be due to
the presence of the cyanoacetyl moiety. (iii) Compounds
6 and 7 have good antioxidant activities that may be attrib-
uted to cycloalka[b]thiophene moiety. The antioxidant ac-
tivities of compounds 6 and 7 follow the order 7 >6,
which may be explained by ring size. And, (iv) compounds
7 and 30 exhibited better antioxidant activity than ascorbic
acid, which may be explained by presence of cyclohepta[b]
thiophene and chromene moiety, respectively (Fig. 1).
total antioxidant potential of resinous exudates from
Heliotropium species, and a comparison of the ABTS
methods.
The rate and/or the extent of the process measured in
terms of the decrease in X′ concentration would be related
to the ability of the added compounds to trap free radicals.
The decrease in color intensity of the free radical solution
due to scavenging of the free radical by the antioxidant ma-
terial is measured calorimetrically at a specific wavelength.
The assay employs the radical cation derived from ABTS
as stable free radical to assess antioxidant potential of the
investigated compounds.
Some of the compounds displayed antioxidant activity
compared with ascorbic acid, as shown in Table 1. Com-
pounds 3, 7, and 30 displayed high antioxidant potency,
while compounds 6, 25, 35, and 37 showed moderate anti-
oxidant activity; the remaining compounds showed weak
antioxidant activity. Compounds 7 and 30 exhibited the
highest antioxidant activity comparable with that of ascor-
bic acid.
Bleomycin-dependent DNA damage assay.
The
bleomycin is a family of glycopeptide antibiotics that was
used routinely as antitumor agents. The bleomycin assay
was adopted for assessing the prooxidant effects of food
antioxidants. The antitumor antibiotic bleomycin binds
iron ions and DNA. The bleomycin–iron complex
degrades DNA that, upon heating with thiobarbituric acid
(TBA), yields a pink chromogen. Upon the addition of
suitable reducing agents, antioxidants compete with DNA
and diminish chromogen formation [39].
CONCLUSION
The objective of the present study was to synthesize and
evaluate the antioxidant activity of some novel thiphene,
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M. A. Gouda
Vol 000
pyrazole, chromene, and pyrazolotriazine derivatives bear-
ing a biologically active sulfonamide moiety with the hope
of discovering new structure serving as antioxidant agent.
The data showed clearly that most of compounds displayed
good to moderate in vitro antioxidant activities.
C16H19N3O3S2 (365.47): C, 52.58; H, 5.24; N, 11.50 %;
found: C, 52.64; H, 5.32; N, 11.55%.
Compound 7: (82%); mp 215°C; pale yellow; IR (KBr):
(ν/cmꢀ1), 3371, 3316, 3235 (NH, NH2), 2929, 2854 (CH
1
aliph) 1661 (CO), 1317, 1157 (SO2); H-NMR (DMSO-
d6) δ. 1.65–1.70 (2H, m, CH2), 1.73–1.75 (2H, m, CH2),
2.46–2.49 (2H, m, CH2), 2.65–2.67 (2H, m, CH2), 6.77
(br, 2H, NH2), 7.64–7.72 (m, 4H, Ar–H), 8.66 (br, 2H,
NH2), 10.20 (1H, br, NH). 13C NMR (DMSO-d6) δ.
[22.4, 22.6, 24.1, 26.0, 4 CH2], 109.0 (Cꢀ3), 118.7 (C2′, 6′),
126.5 (2C, C3′, 5′), 127.9 (C4) 129.4 (C4′), 137.2 (C1′),
142.0 (C5), 159.3 (C2), 164.3 (CO); ms: (m/z, %): 351
(M+, 0.2), 279 (5.2), 233 (26.0), 223 (8.5), 172 (23.0),
156 (23.8), 153 (100), 140 (10.6), 125 (42.6), 92 (67.2),
65 (52.6), 57 (11.0). Anal. Calcd for C15H17N3O3S2
(351.44): C, 51.26; H, 4.88; N, 11.96%; found: C,
51.18; H, 4.93; N, 11.89%.
EXPERIMENTAL
All melting points are in degree centigrade (uncorrected)
and were determined on Gallenkamp electric melting point
apparatus. TLC analysis was carried out on silica gel 60
F254 (Merck, USA) precoated aluminum sheets. The IR
spectra were recorded (KBr) on a Nicolet i55 FTIR spec-
trophotometer (USA) (λ, cmꢀ1) in Faculty of Science and
1
Arts, Ulla, Taibah University, KSA. H-NMR/13C-NMR
spectra were determined on a Bruker spectrophotometer
(USA) at 600 and 150 MHz, respectively, using TMS as
an internal reference and DMSO-d6 as solvent and were
carried out in the King Abdulaziz University, KSA. The
mass spectra (EI) were recorded on JEOL-JMS 600 at
Assiut University, Assiut, Egypt. Elemental analyses
(Japan) (C, H, and N) were carried out on a Yanaco CHNS
Corder elemental analyzer (Japan) at the Microanalytical
Center, Cairo University, Giza, Egypt. The elemental anal-
yses were found to agree favorably with the calculated
values. Biological activities were carried out in Pharma-
cognosy Department, Faculty of Pharmacy, Mansoura Uni-
versity, Mansoura, Egypt.
General procedure for synthesis of 4-amino-5-acetyl-N-[4-
(aminosulfonyl)phenyl]-2-(phenylamino)thiophene-3-carboxamide
(13) and 4-amino-5-benzoyl-N-[4-(aminosulfonyl)phenyl]-2-
(phenylamino)thiophene-3-carboxamide (14).
To
a
suspension of 2-cyano-3-mercapto-N-[4-(aminosulfonyl)
phenyl]-3-(phenylamino)acrylamide (9) (1.87g, 5 mM) in
DMF (40 mL) containig triethylamine (1.01g, 10mM),
1-chloropropan-2-one (0.46g, 5 mM) or 2-chloro-1-
phenylethanone (0.71g, 5 mM) was added. The mixture
was refluxed for 6 h. The reaction mixture was poured
into 50mL of cold water. The resultant solid products
were collected by filtration and recrystallized from a
mixture of EtOH/DMF (4:1) to give compounds 13 and 14.
Compound 13: (66%); mp 260°C; white powder; IR
(KBr): (ν/cmꢀ1), 3356, 3288, (2NH2), 16675, 1628
(2CO), 1523 (N¼N), 13295, 1159 (SO2); 1H-NMR
(DMSO-d6) δ. 2.49 (s, 3H, CH3), 6.60 (br, 2H, NH2),
6.84–7.73 (m, 12H, Ar–H, NH2, NH), 8.25 (1H, br, NH
CO). 13C-NMR (DMSO-d6) δ. 14.3, 116.3, 118.6 (2C),
126.4, 126.5 (2C), 128.5 (2C), 129.5, (2C), 136.1, 137.4,
137.9, 141.8, 164.6, 166.3 (CO); ms: (m/z, %): 432.9
(M+ +2, 0.2), 409 (2.0), 241 (11.3), 215 (46.5) 214 (100),
213 (80.9), 198 (54.5), 182 (68.3), 135 (18.1), 117
(38.2), 86 (55.2), 76 (58.2), 63 (28), 51 (44.1). Anal. Calcd
for C19H18N4O4S2 (430.5): C, 53.01; H, 4.21; N, 13.01%;
found: C, 53.17; H, 4.29; N, 12.95%.
Compound 14: (72%); mp 274°C; pale yellow powder;
IR (KBr): (ν/cmꢀ1), 3356, 3288, (2 NH2), 16675, 1628
(2CO), 1523 (N¼N), 13295, 1159 (SO2); 1H-NMR
(DMSO-d6) δ. 6.77 (br, 2H, NH2), 6.84–7.90 (m, 17H,
Ar–H, NH2, NH) 8.21 (1H, br, NHCO). 13C-NMR
(DMSO-d6) δ. 67.1, 116.3, 107.7, 118.7 (2C), 126.5 (2C),
127.8, 128.8, 128.9 (2C), 129.2 (2C), 129.3 (2C), 129.4
(2C) 130.3, 136.1, 137.4, 137.5, 141.7, 142.3, 161.9,
164.6, 166.1 (CO); ms: (m/z, %): 473 (M+ –[NH3, +H],
0.2), 277 (20.1), 276 (100), 249 (11.4), 198 (19.7), 172
(12.8), 134 (49.3), 90 (22.5), 77 (15.1), 63 (4.9), 51
General procedure for synthesis of 2-amino-N-[4-(amino-
sulfonyl)phenyl]-5,6,7-,8-tetrahydro-4H-cyclohepta[b]thiophene-
3-carboxamide (6) and 2-amino-N-[4-(aminosulfonyl)phenyl]-
4,5,6,7-tetrahydrobenzo-[b]thiophene-3-carboxamide (7). To
a solution of compound 3, 2.39g, 10mM in absolute ethanol
(25 mL) contained morpholine (1 mL), cycloheptanone
(1.12 g, 0.01 mol) or cyclohexanone (0.98g, 10 mM) and
elemental sulfur (0.35, 11 mM) were added. The reaction
mixture was heated under reflux for 5 h, then allowed to
cool, and then poured into ice/water, and the formed solid
product was collected by filtration and recrystallized from
ethanol/benzene to give compounds 6 and 7, respectively.
Compound 6: (80%); mp 265°C; brown crystals; IR
(KBr): (ν/cmꢀ1), 3303, 3286 (NH, NH2), 2913, 2859 (CH
1
aliph) 1655 (CO), 1337, 1160 (SO2); H-NMR (DMSO-
d6): δ. 1.54–1.58 (2H, m, CH2), 1.71–1.72 (4H, m, CH2),
2.48–2.49 (2H, m, CH2), 2.67–2.69 (2H, m, CH2), 6.82
(br, 2H, NH2), 7.25–7.75 (m, 6H, Ar–H, NH2), 10.62
(1H, s, NH); 13C NMR (DMSO-d6) δ. [ 23.0, 27.4, 28.4,
28.5, 31.5, 5 CH2], 118.7 (C3), 119.1 (C2′,6′), 126.4 (C4),
126.5 (2C, C3′, 5′), 136.0 (C4′), 138.7 (C1′), 140.9 (C5),
162.9 (C2), 164.5 (CO); ms: (m/z, %): 365 (M+, 0.2), 333
(4.1), 330 (11.7), 329 (74.4), 281 (18.5), 270 (12.6), 173
(9.4), 172 (100), 157 (62.0), 130 (38.8), 97 (31.9), 87
(44.2), 83 (85.3), 65 (30.8), 57 (11.0). Anal. Calcd for
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Month 2015
Novel Bioactive Sulfonamides
(11.2). Anal. Calcd for C24H20N4O4S2 (492.57): C, 58.52;
H, 4.09; N, 11.37%; found: C, 58.57; H, 4.01; N, 11.43%.
General procedure for synthesis of (E) 2-cyano-N-[4-
(aminosulfonyl) phenyl]-3-(4-(-2-(4-amino-sulfonylphenylcar
bamoyl)-2-cyanovinyl)phenyl)acrylamide (18), (E)-3-(5-chloro-
3-methyl-1-phenyl-1H-pyrazol-4-yl)-2-cyano-N-[4-(aminosulfonyl)
phenyl] acrylamide (19), (E)-2-cyano-N-[4-(aminosulfonyl)
phenyl]-3-(4-(piperidin-1-yl)phenyl)acrylamide (20), and
3-imino-N-[4-(aminosulfonyl)phenyl]-3H-benzo[f]chromene-
2-carboxamide (30). A mixture of 3 (2.39g, 10mM) and
terephthalaldehyde (15) (0.67 g, 5mM) or 5-chloro-3-
methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (16) (2.20 g,
10 mM) or 4-(piperidin-1-yl)benzaldehyde (17) (1.89 g,
10 mM) or 2-hydroxynaphthalene-1-carbaldehyde (29)
(1.72 g, 10 mM) in pyridine (15 mL) was refluxed on
water bath for 10 h and poured into ice water, and the
resultant solid was filtered and recrystallized the proper
solvent to give 18–20 and 30.
Compound 18: (90%); mp >315°C; crystallized from
DMF; yellow crystals; IR (KBr): (ν/cmꢀ1), 3338, 3260
(2NH), 2215 (CN), 1687, 1668 (2CO) 1326, 1157 (SO2);
1H-NMR (DMSO-d6) δ. 6.94 (br, 4H, 2NH2), 7.22–7.24
(m, 4H, Ar–H), 7.78–8.01 (m, 8H, Ar–H), 8.24 (s, 1H,
¼CH), 8.25 (s, 1H, ¼CH), 10.30 (1H, br, NH), 10.32
(1H, br, NH). 13C-NMR (DMSO-d6) δ. 109.7 (2C), 116.2
(2C), 120.1 (2C), 120.2 (2C), 123.4 (2C), 126.4 (2C),
129.7 (2C), 130.4, 130.5, 135.6, 139.5, 149.2, 161.4
(CO); ms: (m/z, %): 486 (M+–[2NH3+2HCN], 3.2), 252
(13.3), 234 (15.0), 219 (6.0), 45 (25.8), 41 (100). Anal.
Calcd for C26H19N5O6S2 (561.59): C, 55.61; H, 3.41; N,
12.47%; found: C, 55.54; H, 3.34; N, 12.50%.
Compound 19: (81%); mp 250°C; crystallized from
EtOH; yellow powder; IR (KBr) (ν/cmꢀ1), 3370, 3316
(NH), 2210 (CN), 1684 (CO), 1311, 1157 (SO2); 1H NMR
(DMSO-d6) δ. 2.43 (s, 3H, CH3), 6.91 (br, 2H, NH2),
7.40–7.80 (m, 9H, Ar–H), 8.10 (s, 1H, ¼CH), 10.10 (1H,
br, NH). 13C-NMR (DMSO-d6) δ. 14.6, 112.7, 115.5,
120.3, 124.5, 126.4, 128.7, 128.8, 136.8, 139.1, 140,
142.4, 149.4, 159.6 (CO); ms: (m/z, %):441 (M, 0.1), 406
(30.8), 358 (14.8), 270 (13.7), 251 (58.4), 185 (10.8), 172
(59.0), 119 (19.6), 98 (10.4), 91 (26.3), 82 (53.9),71 (69.1),
57 (100). Anal. Calcd for C20H16ClN5O3S (441.89): C,
54.36; H, 3.65; Cl, 8.02; N, 15.85%; found: C, 54.36; H,
3.65; Cl, 8.02; N, 15.85%.
153.3 (CH¼),161.3 (CO); ms: (m/z, %):410 (M+, 0.9),
407 (8.3), 313 (11.0), 238 (25.3), 223 (5.4), 212 (32.2),
172 (91.4), 156 (68.4), 140 (8.4), 97 (56.5), 87 (100), 65
(62.5). Anal. Calcd for C21H22N4O3S (410.14): C, 61.44;
H, 5.40; N, 13.65%; found: C, 61.37; H, 5.36; N, 13.60%.
Compound 30: (78%); mp 317°C; crystallized from DMF;
yellowish green crystal; IR (KBr): (ν/cmꢀ1), 3289, 3157
(2NH, NH2), 1682, (CO), 1623 (C¼N), 1365, 1164 (SO2);
1H-NMR (DMSO-d6) δ. 6.87 (br, 2H, NH2), 7.29–8.21 (m,
11H, Ar–H), 9.22 (s, 1H, ¼NH), 13.05 (1H, br, NH).
13C-NMR (DMSO-d6) δ. 115.4, 118.5, 118.7, 119.2 (2C),
121.1, 124.0, 125.6, 126.8 (2C), 128.4, 128.6, 128.8,
129.2, 129.7, 134.3, 137.6, 138.6, 141.1, 153.5, 156.7,
160.3 (CO); ms: (m/z, %): 393 (M+, 2.2), 324 (3.8), 282
(4.9), 239 (2.2), 221 (100), 193 (34.4), 172 (39.8), 164
(30.8), 156 (25.3), 144 (35.5), 105 (17.0), 87 (21.9), 77
(10.0), 65 (13.7). Anal. Calcd for C20H15N3O4S (393.42):
C, 61.06; H, 3.84; N, 10.68%; found: C, 61.12; H, 3.78; N,
10.77%.
General procedure for synthesis of (E)-2-cyano-3-(3-methyl-1-
phenyl-5-(piperidin-1-yl)-1H-pyrazol-4-yl)-N-[4-(aminosulfonyl)
phenyl]acrylamide (24) and (E)-2-cyano-3-(3-methyl-5-mor-
pholino-1-phenyl-1H-pyrazol-4-yl)-N-[4-(aminosulfonyl)phe-
nyl]xacrylamide (25). General procedure. A mixture of
3 (2.39 g, 10mM), 5-chloro-3-methyl-1-phenyl-1H-pyrazole-
4-carbaldehyde (16) (2.20g, 10 mM), and piperidine (2.55 g,
30 mM) or morpholine (2.61 g, 30 mM) in ethanol (40mL)
was refluxed on water bath for 8 h and poured into ice
water, and the resultant solid was filtered and crystallized
from EtOH/benzene to give 24 and 25.
Compound 24: (64%); mp 200°C; yellow powder; IR
(KBr): (ν/cmꢀ1), 3338, 3242 (2NH2, NH), 2205 (CN), 1661
1
(CO) 1317, 1155 (SO2); H-NMR (DMSO-d6) δ. 1.16–1.32
(m, 2H, CH2), 2.05–2.49 (m, 4H, 2CH2), 2.87 (s, 3H, CH3),
2.94–3.06 (m, 4H, 2CH2), 6.66 (br, 2H, NH2), 7.22–7.79
(m, 9H, Ar–H), 8.18 (s, 1H, ¼CH), 9.51 (1H, br, NH); ms:
(m/z, %): 473 (M+–NH3, 1.0), 367 (0.8), 254 (31.2), 243
(21.5), 185 (12.5), 172 (100) 156 (53.3), 92 (57.4), 77
(96.1), 65 (43.4). Anal. Calcd for C25H26N6O3S (490.58): C,
61.21; H, 5.34; N, 17.13%; found: C, 61.21; H, 5.34; N,
17.13%.
Compound 25: (68%); mp 185°C; yellow powder; IR
(KBr): (ν/cmꢀ1), 3294, 3244 (2NH2, NH), 2209 (CN), 1661
1
(CO) 1334, 1156 (SO2); H-NMR (DMSO-d6) δ. 2.87 (s,
Compound 20: (90%); mp 290°C; crystallized from
EtOH; Orange crystals; IR (KBr): (ν/cmꢀ1), 3338, 3321,
3257 (NH, NH2), 2938, 2837 (CH aliph), 2204 (CN),
3H, CH3), 2.94–2.98 (m, 4H, 2CH2), 3.52–3.72 (m, 4H,
2CH2), 7. 22 (br, 2H, NH2), 7.34–7.79 (m, 9H, Ar–H), 8.18
(s, 1H, ¼CH), 9.51 (1H, br, NH); ms: (m/z, %): 473
(M–[NH3+H2], 0.8), 367 (0.9), 366 (38.7), 358 (15.3), 342
(19.5), 294 (8.6), 243 (21.5), 185 (20.8), 71 (69.1), 172
(100), 156 (53.3), 108 (32.1), 92 (57.4), 77 (96.1), 65 (43.4).
Anal. Calcd for C24H24N6O4S (492.55): C, 58.52; H, 4.91;
N, 17.0%; found: C, 58.52; H, 4.91; N, 17.0%.
1
1674 (CO), 1314, 1184 (SO2); H-NMR (DMSO-d6) δ.
1.54–1.60 (2H, m, CH2), 3.21–3.23 (2H, m, CH2), 3.35–
3.40 (2H, m, CH2), 6.78 (br, 2H, NH2), 6.80–7.82 (m,
8H, Ar–H), 7.99 (s, 1H, ¼CH), 10.58 (1H, br, NH). 13C-
NMR (DMSO-d6) δ. 96.8, 112.9 (2C, C-3′,5′), 117.6
(CN), 119.5 (2C, C-3,5), 126.4 (2C, C-3′,5′), 126.5 (C-
1′), 133.2 (C-2,6), 138.4 (C-1), 141.3 (C-4), 151.7 (C-4′),
Synthesis of 6-amino-3-methyl-1-phenyl-N-[4-(aminosulfonyl)
phenyl]-1H-pyrazolo-[3, 4-b]pyridine-5-carboxamide (28).
A
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. A. Gouda
Vol 000
suspension of 3 (2.39 g, 10mM), 5-chloro-3-methyl-1-
phenyl-1H-pyrazole-4-carbaldehyde (16) (2.20g, 10mM),
and ammonium acetate (6.93, 90mM) in ethanol (40 mL)
was refluxed on water bath for 8h and poured into ice
water, and the resultant solid was filtered and recrystallized
the proper EtOH/ benzene to give 28. (76%); M. p. 250°C;
yellow crystal; IR (KBr): (ν/cmꢀ1), 3338, 3246 (2NH2),
1663 (CO) 1312, 1159 (SO2); 1H-NMR (DMSO-d6) δ. 2.48
(s, 3H, CH3), 6.72 (br, 2H, NH2), 7.38–7.79 (m, 9H,
Ar–H), 8.13 (s, 1H, ¼CH), 9.83 (br, 1H, NH); ms: (m/z,
%):405 (M–NH3, 10.9), 240 (100), 185 (9.7), 174 (8.8),
87 (11.0), 156 (5.0) 71 (12.2), 57 (19.1). Anal. Calcd for
C20H18N6O3S (422.12): C, 56.86; H, 4.29; N, 19.89, %;
found: C, 56.86; H, 4.29; N, 19.89%.
Compound 36: (90%); mp 315°C; reddish-violet pow-
der; IR (KBr): (ν/cmꢀ1), 3389, 3322, 3245, 3180 (4NH,
NH2), 2205 (CN), 1667 (CO), 1617 (C¼N), 1525
1
(N¼N), 1329, 1156 (SO2); H-NMR (DMSO-d6) δ. 6.83
(br, 2H, NH2), 7.09–7.90 (m, 10H, Ar–H), 8.39 (br, 1H,
NH, indol), 8.99 (br, 1H, NH pyrazole), 10.46 (1H, br,
NH-CO), 11.10 (1H, br, ). 13C-NMR (DMSO-d6) δ. 93.7,
107.7, 111.5, 117.8, 119.2 (2C), 119.7, 120.1, 121.0,
121.9,124.7, 125.8, 126.6 (2C) 136.5, 138.2, 140.5,
140.9, 149.7, 154.8, 164.3 (CO); ms: (m/z, %): 449 (M+
+1, 2.2), 209 (12.7), 172 (80.8), 156 (42.4), 142 (100)
119 (5.4), 105 (13.4), 87 (37.1), 77 (65.5), 45 (63.8). Anal.
Calcd for C20H16N8O3S (448.46) C, 53.56; H, 3.60; N,
24.99%; found: C, 53.56; H, 3.60; N, 24.99%.
General procedure for synthesis of 2,3-dimethyl-5-oxo-1-
phenyl-pyrazol-4-yl)hydrazono-3-(4-(aminosulfonyl)2-(2-phenyl-
amino)-3-oxopropanenitrile (35), 2-(2-(3-(1H-indol-3-yl)-1H-
pyrazol-5-yl)hydrazono)-3-(4-(aminosulfonyl)phenylamino)-
3-oxopropanenitrile (36), 2-(2-(4,6-dimethyl-2H-pyrazolo[3,4-b]
pyridin-3-yl)hydrazono)-3-(4-aminosulfonyl) phenylamino)-
3-oxopropanenitrile (37), 2-(2-{4-((1,5-dimethyl-3-oxo-2-phenyl-
2,3-dihydro-1H-pyrazol-4-yl)-diazenyl)-5-methyl-1H-pyrazol-3-
yl}hydrazono)-3-(4-(aminosulfonyl) phenylamino)-3-oxopro-
Compound 37: (85%); mp > 315°C; reddish-violet crys-
tals; IR (KBr): (ν/cmꢀ1), 3325, 3241, 3193 (2NH, NH2),
2203 (CN), 1675 (CO), 1638 (C¼N), 1527 (N¼N), 1315,
1
1154 (SO2); H-NMR (DMSO-d6) δ. 2.69 (s, 3H, CH3),
2.96 (s, 3H, CH3), 6.91 (br, 2H, NH2), 7.00 (s, 1H, Ar–
H), 7.81–7.95 (m, 4H, Ar–H), 9.21 (br, 1H, NH pyrazole),
10.82 (br, 1H, NHCO), 14.29 (1H, br, NH hydrazo).
13C-NMR (DMSO-d6) δ. 18.7, 22.7, 112.1, 119.4, 119.6
(2C), 119.7, 126.4, 126.6 (2C), 138.7, 140.4, 140.6,
144.1, 163.5 (CO); ms: (m/z, %): 265 (M+–[4,6-dimethyl-
1H-pyrazolo[3,4-b] pyridine], 0.3), 222 (11.9), 221 (100),
193 (26.8), 172 (55.7), 164 (22.0), 156 (17.7), 144
(66.5), 115 (‵18.5), 92 (20.4), 74 (19.1), 63 (23.2). Anal.
Calcd for C17H16N8O3S (412.43): C, 49.51; H, 3.91; N,
27.17%; found: C, 49.51; H, 3.91; N, 27.17%.
panenitrile (38).
A well-stirred solution of 4-amino-
1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one (31) (1.02 g,
5mM), 5-amino-3-(1H-indol-3-yl)-1H-pyrazole (32) (0.99 g,
5mM), 3-amino-4,6-dimethyl-2H-pyrazolo[3,4-b]pyridine
(33) (0.81 g, 5 mM), or 4-(5-amino-3-methyl-1H-pyrazol-4-yl
diazenyl)-2,3-dimethyl-1-phenyl-1,2-dihydropyrazol-5-one (34)
(1.60 g, 5 mM) in a mixture of acetic acid (10mL) and
concentrated HCl) 4 mL) was cooled in an ice bath, and then
a solution of sodium nitrite (0.4 g, 5.8 mM in 5 mL H2O) was
added dropwise under stirring. The aforementioned cooled
diazonium solution was added slowly to a well-stirred
solution of 3 (1.20 g, 5 mM) in pyridine (25mL). The
reaction mixture was stirred for a further 2 h. The crude
product was filtered off, dried well, and crystallized from a
mixture of EtOH/DMF to give compounds pyrazoles 35, 36,
37, and 38, respectively.
Compound 38: (78%); mp 275°C; reddish-brown crys-
tals; IR (KBr): (ν/cmꢀ1), 3389, 3294, 3185 (2NH, 2NH),
2205 (CN), 1665, 1625 (2CO), 1617 (C¼N), 1525
1
(N¼N), 1320, 1158 (SO2); H-NMR (DMSO-d6) δ. 2.49
(s, 3H, CH3, antipyrine), 2.62 (s, 3H, CH3, pyrazole)
3.28 (s, 3H, CH3–N), 7.01 (br, 2H, NH2), 7.25–7.95 (m,
9H, Ar–H), 10.40 (1H, br, NH pyrazole). 10.98 (1H, br,
NH CO), 12.75 (1H, br, NH hydrazo); ms: (m/z, %): 449
(M+–[2CH4+NH2SO2], 0.6), 335 (1.8.), 215 (1.3), 201
(8.9), 172 (14.6), 156 (5.5), 119 (11.5), 88 (100), 76
(15.6), 65 (20.0), 40 (13.4). Anal. Calcd for C24H23N11O4S
(561.58): C, 51.33; H, 4.13; N, 27.44%; found: C, 51.33;
H, 4.13; N, 27.44%.
Compound 35: (88%); mp 280°C; reddish-brown crys-
tals; IR (KBr): (ν/cmꢀ1), 3315, 3247, 3180 (2NH, NH2),
2210 (CN), 1675, 1637, (2CO), 1526 (N¼N), 1316, 1155
1
(SO2); H-NMR (DMSO-d6) δ. 2.31 (s, 3H, CH3, antipy-
General procedure for the synthesis of pyrazolotriazines
39–41. A suspension of arylazo derivatives 36, 37, and
38 (3mM) in a mixture of Ac OH (10 mL) and DMF
(5 mL) was refluxed for 7 h. The reaction mixture was
poured into ice cold water, and then the formed
precipitate was filtered off, dried, and recrystallized from
DMF to give compounds 39, 40, and 41, respectively.
7--Indol-3-yl)-pyrazolo[5,1-c][1,2,4]-triazine-3-carboxylic
rine), 3.11 (s, 3H, CH3–N), 7.00 (br, 2H, NH2),
7.25–7.78 (m, 9H, Ar–H), 10.92 (br, 1H, NH), 12.03
(1H, br, NH hydrazo). 13C-NMR (DMSO-d6) δ. 12.6,
39.4, 112.6, 117.3, 119.2 (2C), 119.8, 120.0, 121.0,
123.8, 126.4 (2C), 128.9, 134.1, 136.8, 138.4, 160.1,
160.6 (CO); ms: (m/z, %): 405 (M+ꢀ[SO], 0.3), 264
(12.0), 213 (10.9), 198 (2.9), 188 (32.0), 173 (16.0), 172
(100), 156 (49.9), 97 (40.4), 87 (61.4), 105 (17.0), 77
(34.4), 56 (24.0), 52 (22.3). Anal. Calcd for C20H19N7O4S
(453.47): C, 52.97; H, 4.22; N, 21.62%; found: C, 52.97;
H, 4.22; N, 21.62%.
acid(N-[4-(aminosulfonyl)phenyl])-amide] (39).
(79%);
mp > 315°C; reddish-brown powder; IR (KBr): (ν/cmꢀ1),
3390, 3325, 3245 (2NH, NH), 1667 (CO), 1618 (C¼N),
1
1528 (N¼N), 1329, 1157 (SO2); H-NMR (DMSO-d6) δ.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Novel Bioactive Sulfonamides
6.79 (br, 2H, NH2), 7.09–8.37 (m, 10H, Ar–H) 8.98 (br,
1H, NH, indol), 8.99 (br, 2H, NH2), 10.41 (1H, br, NH
indole). 11.05 (1H, br, NH CO). 13C-NMR (DMSO-d6)
δ. 93.8, 107.7, 111.5, 117.8, 119.1 (2C), 120.1, 120.1,
121.0, 121.9, 124.7, 124.7, 125.7, 126.6 (2C) 136.5,
138.1, 140.5, 140.8, 154.8, 164.2 (CO); ms: (m/z, %):
449 (M+ +1, 5.2), 209 (8.0), 197 (33.7), 172 (100), 156
(51.8), 142 (34.4), 119 (2.7), 105 (1.8), 87 (54.9), 65
(8.3), 45 (41.1). Anal. Calcd for C20H16N8O3S (448.46):
C, 53.56; H, 3.60; N, 24.99%; found: C, 53.56; H, 3.60;
N, 24.99%.
ð%Þ Inhibition ¼ ½A ðcontrolÞ – A ðtestÞ =A ðcontrolÞꢁ ꢂ 100
Ascorbic acid (20 mL, 2 mM) solution was used as a
standard antioxidant (positive control). Blank sample was
run using solvent without ABTS (Table 1).
Bleomycin-dependent DNA damage assay [38,39]. To the
reaction mixtures in a final volume of 1.0 mL, the following
reagents at the final concentrations stated were added: DNA
(0.2 mg/mL), bleomycin (0.05 mg/mL), FeCl3 (0.025mM),
magnesium chloride (5 mM), KH2PO4/KOH buffer pH 7.0
(30 mM), and ascorbic acid (0.24 mM) or the test fractions
diluted in MeOH to give a concentration of (0.1 mg/mL).
The reaction mixtures were incubated in a water bath at
37°C for 1h. At the end of the incubation period, 0.1mL
of ethylenediaminetetraacetic acid (EDTA) (0.1 M) was
added to stop the reaction (the iron EDTA complex is
unreactive in the bleomycin assay). DNA damage was
assessed by adding 1 mL 1% (w/v) TBA and 1 mL of 25%
(v/v) hydrochloric acid (HCl) followed by heating in a
water bath maintained at 80°C for 15min. The chromogen
formed was extracted into 1-butanol, and the absorbance
was measured at 532nm.
8-Amino-2,4-dimethyl-1,5,6,8a,9-pentaazafluorene-7-carboxylic
acid (N-[4-(aminosulfonyl)phenyl])-amide [40].
(68%);
mp>315°C; green powder; IR (KBr) (ν/cmꢀ1), 3327,
3193, 3175 (2NH, NH2), 1676 (CO), 1636 (C¼N), 1525
1
(N¼N), 1374, 1153 (SO2); H-NMR (DMSO-d6) δ. 2.63
(s, 3H, CH3), 2.90 (s, 3H, CH3), 6.92 (br, 2H, NH2), 6.99
(s, 1H, Ar–H), 7.45 (br, 2H, NH2), 7.66–7.93 (m, 4H, Ar–
H), 10.78 (br, 1H, NHCO). 13C-NMR (DMSO-d6) δ. 18.7,
25.4, 119.4 (2C), 121.2, 126.6 (2C), 138.6, 140.4, 140.6,
143.9, 144.3, 160.5, 163.7, 164.9 (CO); ms: (m/z, %): 412
(M+, 0.3), 389 (7.0), 361 (9.4), 314 (100), 239 (11.4), 215
(1.2), 172 (8.0), 119 (3.7), 94 (1.8), 76 (6.9), 56 (1.4).
Anal. Calcd for C20H16N8O3S (448.46): C, 53.56; H, 3.60;
N, 24.99%; found: C, 53.56; H, 3.60; N, 24.99%.
Acknowledgments. We deeply appreciate the assistance of Mister
Ahmed Abass, Pharmacognosy Department, Faculty of Pharmacy,
Mansoura University, Mansoura, Egypt, for screening the
biological activities of the tested compounds.
4-Amino-8-((2,3-dimethyl-5-oxo-1-phenyl-2,5-dihydro-1H-
pyrazol-4-yl)diazenyl)-7-methyl-pyrazolo[5,1-c]-[1,2,4]triazine-3-
carboxylic acid (N-[4-(aminosulfonyl)phenyl])-amide (41). (82%);
mp >315°C; scarlet-red crystals; IR (KBr) (ν/cmꢀ1),
3356, 3288, (2 NH2), 1665, 1628 (2CO), 1525 (N¼N),
REFERENCES AND NOTES
1
1325, 1159 (SO2); H-NMR (DMSO-d6) δ. 2.49 (s, 3H,
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CH3, antipyrine), 2.65 (s, 3H, CH3, pyrazole), 3.30 (s,
3H, CH3–N), 6.73 (br, 2H, NH2), 7.30–8.87 (m, 11H,
Ar–H, NH2), 10.46 (1H, br, NH CO); ms: (m/z, %): 448
(M+–[2CH3+NH3, +SO2],0.2), 214 (7.8), 188 (11.1),
172 (5.4), 119 (4.0), 105 (0.5), 88 (13.7), 73 (100), 60
(14.8), 45 (99.3). Anal. Calcd for C24H23N11O4S
(561.58): C, 51.33; H, 4.13; N, 27.44; found: C, 51.33;
H, 4.13; N, 27.44.
ABTS screening assay [32]. Antioxidant activities were
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azino-bis(3-ethyl benzothiazoline-6-sulfonic acid)] was
prepared by reaction of ABTS (60 mL) with MnO2
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(pH 7). After shaking the solution for a few minutes, it
was centrifuged and filtered. The absorbance (A control)
of the resulting green-blue solution (ABTS radical
solution) was recorded at λmax 734 nm. The absorbance
(A test) was measured upon the addition of (20 mL of
1 mg/mL) solution of the tested sample in spectroscopic
grade MeOH/buffer (1:1v/v) to the ABTS solution. The
inhibition ratio (%) was calculated using the following
formula:
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. A. Gouda
Vol 000
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet